| Literature DB >> 25066127 |
Rachel Deplus1, Loïc Blanchon1, Arumugam Rajavelu2, Abdelhalim Boukaba1, Matthieu Defrance1, Judith Luciani1, Françoise Rothé3, Sarah Dedeurwaerder1, Hélène Denis1, Arie B Brinkman4, Femke Simmer4, Fabian Müller5, Benjamin Bertin1, Maria Berdasco6, Pascale Putmans1, Emilie Calonne1, David W Litchfield7, Yvan de Launoit8, Tomasz P Jurkowski2, Hendrik G Stunnenberg4, Christoph Bock9, Christos Sotiriou3, Mario F Fraga10, Manel Esteller11, Albert Jeltsch12, François Fuks13.
Abstract
DNA methylation is a central epigenetic modification that is established by de novo DNA methyltransferases. The mechanisms underlying the generation of genomic methylation patterns are still poorly understood. Using mass spectrometry and a phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates endogenous Dnmt3a at two key residues located near its PWWP domain, thereby downregulating the ability of Dnmt3a to methylate DNA. Genome-wide DNA methylation analysis shows that CK2 primarily modulates CpG methylation of several repeats, most notably of Alu SINEs. This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. By revealing phosphorylation as a mode of regulation of de novo DNA methyltransferase function and by uncovering a mechanism for the regulation of methylation at repetitive elements, our results shed light on the origin of DNA methylation patterns.Entities:
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Year: 2014 PMID： 25066127 DOI： 10.1016/j.celrep.2014.06.048
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423